ADDITION OF L-GLUTAMINE TO A LINOLEIC-ACID PERIFUSATE PREVENTS THE FATTY ACID-INDUCED DESENSITIZATION OF PANCREATIC-ISLET RESPONSE TO GLUCOSE

Previous studies showed that exposure of pancreatic islets to polyunsa turated fatty acids (PUFA) can render the beta cells unresponsive to g lucose, thus suggesting the possibility that prolonged obligatory use of lipid preparations containing high concentrations of essential fatt y acids during total parenteral nutrition may adversely affect glucose tolerance. In the present study we examined the effect of pretreatmen t of isolated murine islets with 10 mmol/L linoleate (18:2, omega6) al one or in the presence of 20 mmol/L-glutamine on the response of both alpha and beta cells to 27.7 mmol/L glucose perifusion at 37-degrees-C . The incremental areas under the curve/20 mins (AUC/20 mins) for insu lin output stimulated by 27.7 mmol/L glucose were 1552.8 +/- 276.3 pg and 220.4 +/- 163.9 pg (P < 0.001), (n = 6), respectively, before and after treatment with linoleic acid alone. In experiments in which the islets were treated with linoleate in the presence of L-glutamine ther e was no difference in the incremental insulin AUC/20 mins, in respons e to 27.7 mmol/L glucose before and after the fatty acid treatment (20 51.8 +/- 420.5 pg versus 2159.2 +/-317.6 pg, respectively, n = 6). Glu cose-induced suppression of glucagon secretion, which was lost after p erifusion of islets with the fatty acid alone, was observed when gluta mine was added to the linoleate perifusate. In conclusion, the additio n of L-glutamine to linoleic acid perifusion of isolated islets comple tely blocked the PUFA-induced desensitization of both pancreatic alpha and beta cells to glucose effect.